Male reproductive physiology and hypogonadism

Question 1

What 2 structures do the testes contain

Answer 1

seminiferous tubules composed of Sertolli cells and germ cells
Interstitial containing Leydig cells that produce testosterone

Question 2

What stimulates the secretion of GnRH

Answer 2

hypothalamic neurones

Question 3

What stimulates the release of LH and FSH

Answer 3

Pulsatile GnRH

Question 4

How does GnRH stimulate the release of LH and FSH

Answer 4

it binds to receptors on the plasma membrane of pituitary gonadotrophs and stimulates their release by a calcium-dependent mechanism that may involved diacyclglycerol

Question 5

What are LH and DSH composed of

Answer 5

two glucoprotein chains

Question 6

What do LH and FSH do

Answer 6

They interact with cell membrane receptors and stimulate adenylate cyclase

Question 7

What does LH stimulate in males

Answer 7

The production of testosterone by Leydig cells
The synthesis of testoereon by actin gone the steroidogenic acute regulatory protein which delivers cholesterol to the inner mitochondrial membrane where it is converted to pregnenolone

Question 8

Sperm are produced under the stimulation of what

Answer 8

testosterone and FSH

Question 9

What inhibits FSH secretion

Answer 9

inhibin B as well as testosterone and estradiol

Question 10

What modulate GnRH secretion

Answer 10

several hormones, neurotransmitters and cytokines

Question 11

When might testosterone levels be reduced

Answer 11

acute and chronic illnesses and fasting

Question 12

How much plasma testosterone is free (unbound)

Answer 12

2%

Question 13

Some testosterone is bound to a hepatic glycoprotein. What is this called

Answer 13

sex hormone-binding globulin

Question 14

What is the other protein that testoesterone can be bound to

Answer 14

albumin

Question 15

What can cause an increase in SHGB

Answer 15

Ageing 
antiepileptic agents 
liver disease 
oestrogens 
thyrotoxicosis 
growth hormone deficiency

Question 16

What can cause a decrease in SHGB

Answer 16

Diabetes mellitus 
Obesity 
corticosteroids, anabolic steroids 
hypothyroidism 
acromegaly

Question 17

Why is it that changes in the SHBG levels do not affect free androgen levels

Answer 17

Hypothalamic-pituitary system responds to acute changes in the concentrations of bioavailable testosterone by altering testosterone synthesis

Question 18

What are the physiological actions of tester one

Answer 18

The result of the combined effects of testosterone and its active metabolites

Question 19

What are the major functions of androgens in males

Answer 19

regulation of gonadotrophin secretion from the hypothalamic-pituitary system

initiation and maintenance of spermatogenesis

formation of the male genital tract during embryogenesis
development of male secondary sexual characteristics and sexual potency at puberty and their maintenance there after

Question 20

What is male hypogonadism

Answer 20

a syndrome of decreased testosterone production, sperm production or both

Question 21

What might hypogonadism result from

Answer 21

disease of the testes (primary hypogonadism)

disease of the pituitary or hypothalamus (secondary hypogonadism)

Question 22

Why is primary hypogonadism also sometimes known as hypergonadotrophic hypogonadism

Answer 22

reduced testosterone levels result in elevated gonadotrophin levels (negative feedback effect)

Question 23

What are some of the congenital causes of primary hypogonadism

Answer 23

Klinefelter’s syndrome
Cryptorchidism
Other chromosomal abnormalities

Question 24

What is the most common cause of primary hypogonadism

Answer 24

Klinefelter’s syndrome

Question 25

What causes Klinefelter's syndrome

Answer 25

1 or more extra chromosome | This results in damaged seminiferous tubules and Leydig cells

Question 26

What is the most common Klinefelter's genotype and what does it result from

Answer 26

47XXY | Non-disjunction of the sex chromosomes of either parent during meiotic division

Question 27

What are some other symptoms of Klinefelter's syndrome

Answer 27

Intellectual dysfunction and behaviour abnormalities that cause difficulty in social interactions Predisposition to developing chronic bronchitis, bronchiectasis and emphysema, breast cancer, non-Hodgkin's lymphoma, varicose veins, leg ulcer,s diabetes mellitus

Question 28

What does Cryptorchidism refer to

Answer 28

unilateral or bilateral undescended tests (in the abdominal cavity or in the inguinal canal) that cannot be manipulated manually in the scrotum by the age of 1 year

Question 29

What are some acquired causes of primary hypogonadism

Answer 29

``` Infections Testicular trauma or torsion chemotherapy radiotherapy autoimmune damage chronic illness e.g. COPD congestive cardiac failure Crohn's disease coeliac disease chronic liver disease RA chronic kidney disease AIDS ```

Question 30

What is secondary hypogonadism due to

Answer 30

Impaired secretion of hypothalamic GnRH or pituitary gonadotrophins

Question 31

What might congenital secondary hypogonadism be associated with

Answer 31

anosmia in Kallmann's syndrome

Question 32

What is Kallmann's syndrome sometimes associated with

Answer 32

red-green colour blindness midline facial abnormalities (e.g. cleft palate) urogenital tract abnormalities synkinesis (mirror movements of the hands) hearing loss

Question 33

What might secondary hypogonadism be caused by

Answer 33

Any pituitary or hypothalamic disease such as pituitary adenoma, craniopharyngioma, pituitary surgery, infarction, infection, infiltrative disorders such as haemochromatosis, sarcoidosis, histiocytosis, TB and fungal infections

Question 34

What can suppress gonadotrophin secretion

Answer 34

``` chronic systemic illness diabetes mellitus hyperprolactinaemia androgen excess cortisol excess oestrogen excess chronic opiate administration GnRH analogues ```

Question 35

What does the clinical presentation depend on

Answer 35

whether the onset of hypogonadism is before or after puberty

Question 36

What are the clinical presentation of hypogonadism before the onset of puberty

Answer 36

Delayed puberty | Testes

Question 37

What are the clinical presentation of hypogonadism after the onset of puberty

Answer 37

Fatigue, reduced energy and lowered physical strength low mood, irritability and poor concentration reduced libido and/or sexual function. loss of spontaneous morning erections and infertility osteoporosis and fragility fractures Soft tests

Question 38

What is the major action of testosterone on male sexuality

Answer 38

libido

Question 39

What is primary hypogonadism more likely to be associated with

Answer 39

gynaecomastia - due to the stimulation of testicular aromatase activity by the increased serum FSH and LH resulting in increased conversion of testosterone to estradiol and also increased testicular secretion of estradiol relative to testosterone

Question 40

How can a diagnosis of hypogonadism be confirmed

Answer 40

by finding low serum testosterone and or decreased sperm in the semen

Question 41

Describe the variation in levels of serum testosterone

Answer 41

Diurnal variation - maximum at about 9 am and lower levels in the evening

Question 42

What levels of LH and FSH indicate testicular damage (primary hypogonadism)

Answer 42

High concentrations

Question 43

What levels of LH and FSH indicate pituitary or hypothalammic disease

Answer 43

Low or inappropriately normal

Question 44

What should men with primary hypogonadism have done

Answer 44

A peripheral leukocyte karyotype to determine whether Klinefelter's syndrome is present

Question 45

What is the treatment for hypogonadism

Answer 45

Directed at any underlying disorders Relieve symptoms and preserve bone density Pre-puberty boys should be started on low doses of testosterone that are gradually increased

Question 46

Where is testosterone gel applied

Answer 46

Should and upper arm

Question 47

What are some advantages of and disadvantages of the gel

Answer 47

Advantages - self-administration, avoidance of painful injections, dries quickly Disadvantages - could be transferred to partner through skin contact , patients should not shower for 6 hours

Question 48

What are some disadvantages of IM testosterone

Answer 48

Pain at injection site More mood swings Only every 2-3 weeks

Question 49

What are some advantages and disadvantages of subcutaneous testosterone implants

Answer 49

Only every 6 months Minor surgery Complications include infection, bleeding, extrusion and scarring

Question 50

What are some side effects of testosterone replacement

Answer 50

``` Acne on the upper trunk Prostate enlargement Polycythaemia Gynaecomastia Fluid retention Sleep apnoea mood fluctuations ```

Question 51

What are some contraindications of testosterone replacement

Answer 51

``` Prostate cancer Polycythaemia breast carcinoma sleep apnoea conditions in which fluid retention may be harmful ```

Question 52

How are men with secondary hypogonadism who desire fertility treated?

Answer 52

With gonadotrophin replacement or pulsatile GnRH therapy

Question 53

What should be asked about in a follow up appointment

Answer 53

``` Improvements in symptoms Weight gain peripheral oedema gynaecomastia In men over 40, PR exam ```

Question 54

What lab tests should be measured in follow up

Answer 54

Haemoglobin Prostate -specific antigen (PSA) LFT and fasting lipid profile Testosterone levels